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Poor Penetration (poor + penetration)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

The Effects of 5-Aminolevulinic Acid Esters on Protoporphyrin IX Production in Human Adenocarcinoma Cell Lines,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 5 2001
H. Brunner
ABSTRACT Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA),induced protoporphyrin IX (PPIX) is an interesting approach to detect and treat dysplasia and early cancers in the gastrointestinal tract. Because of low lipophilicity resulting in poor penetration across cell membranes, high doses of ALA should be administered in order to reach clinically relevant levels of PPIX. One way of increasing PPIX accumulation is derivatization of ALA into a more lipophilic molecule. In our in vitro study, different esterifications of ALA were investigated to analyze the effects on PPIX accumulation in human adenocarcinoma cell lines. For systematic analysis of cell type,specific PPIX accumulation, three human adenocarcinoma cell lines (SW480, HT29 and CaCo2) and a fibroblast cell line (CCD18) were tested. 3-(4,5-Dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assays were performed to ensure that the ALA esters showed no cellular dark toxicity. Different concentrations (ranging from 0.012 to 0.6 mmol/L, 3 h) and incubation times (5, 10, 30, 180 min; 0.12 mmol/L) were examined. PPIX accumulation was measured using flow cytometry. ALA esters, especially ALA-hexylester and ALA-benzylester, induced significant higher PPIX levels in adenocarcinoma cell lines when compared with ALA and may be promising candidates for PDT and PDD. [source]

Rapid seismic reflection imaging at the Clovis period Gault site in central Texas

ARCHAEOLOGICAL PROSPECTION, Issue 4 2007
John A. Hildebrand
Abstract Using a modified seismic reflection imaging system with rapid translation of receivers, stratigraphic profiles were collected at the Gault site in central Texas. For rapid data collection, spikeless geophone receivers were placed in sand-filled bags at tight spacing, and these receivers were rapidly pulled along the ground surface between shots. Shots were produced by a small hammer strike to a vertical pipe at 20-cm intervals. High quality ultrashallow seismic reflection profiles were collected at a rate of 25,m,h,1, significantly faster than what is possible with conventional seismic reflection imaging using individually planted geophones. Ground-penetrating radar was attempted, but abandoned owing to the poor penetration of the radar signals in the clay soils present at the Gault site. Electromagnetic induction grids were collected surrounding each seismic reflection profile, and provided information on near-surface ground water. Seismic reflection images of Gault site stratigraphy provided greater depth penetration than accessible from backhoe trenching and coring, and helped to better outline the site geological context. Seismic images reveal coherent reflections at shallow depths (0,2.5,m), and extensive scattering at deeper levels (2.5,8,m), underlain by reflection-free zones. These data are interpreted as clay and gravel layers overlaying palaeostream channels carved into the limestone bedrock. Where comparative data were available, the geophysical findings were corroborated by observations of site stratigraphy in archaeological excavation units, backhoe trenches and cores. Seismic reflection studies at the Gault site revealed a palaeochannel filled with pre-Clovis age sediments. Pre-Clovis age sediments are not known to occur at other locations within the Gault site. They provide a unique opportunity to test for cultural remains of great antiquity. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Onychomycosis in clinical practice: factors contributing to recurrence

BRITISH JOURNAL OF DERMATOLOGY, Issue 2003
R.K. Scher
Summary The treatment of onychomycosis has improved in recent years and many patients can now expect a complete and lasting cure. However, for up to 25% of patients, persistent disease remains a problem, thus presenting a particular challenge to the clinician. For these patients, it is obviously important to ensure that a correct diagnosis of onychomycosis has been made, as misdiagnosis will inevitably jeopardize the perception of therapeutic effectiveness. Although onychomycosis accounts for about 50% of all nail diseases seen by physicians, nonfungal causes of similar symptoms include repeated trauma, psoriasis, lichen planus, local tumours vascular disorders and inflammatory diseases. Predisposing factors that contribute to a poor response to topical and/or oral therapy include the presence of a very thick nail, extensive involvement of the entire nail unit, lateral nail disease and yellow spikes. However, poor penetration of systemic agents to the centre of infection, or the inability of topical agents to diffuse between the surface of the nail plate and the active disease below, probably contributes to this. Other factors contributing to recurrence may be related to the patient's family history, occupation, lifestyle or underlying physiology. In addition, patients with concomitant disease (e.g. peripheral vascular disease, diabetes) or patients who are immunosuppressed (e.g. those with human immunodeficiency virus/acquired immunodeficiency syndrome) are more susceptible to onychomycosis. In the elderly, the prevalence of onychomycosis may be as high as 60%, and increases with age; in this population, physical trauma plays a major role in precipitating recurrence, especially in patients with faulty biomechanics due to underlying arthritis and bone abnormalities. It is also possible that recurrence in some cases is due to early termination of treatment or use of an inappropriate dose, and these possibilities should be eliminated before further investigations are undertaken. ,There is good evidence to suggest that a combination of oral and topical therapies, when given at the same time, yield excellent clinical outcomes, although there remains a need for more effective topical agents with greater nail penetration and more effective oral antifungal agents. [source]

Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2002
Nobuyuki Takayama
Summary. A 32-year-old woman with relapsed Philadelphia chromosome-positive acute lymphoblastic leukaemia was treated with imatinib mesylate (formerly STI571), a selective inhibitor of BCR/ABL tyrosine kinase. Although the initial marrow response was good and stably maintained, she subsequently relapsed with extensive infiltration of leukaemic cells into the central nervous system (CNS). After controlling her CNS disease with additional intrathecal chemotherapy, we measured the concentration of imatinib in cerebrospinal fluid (CSF) and blood simultaneously. The concentration of imatinib in CSF was about 92-fold lower than that in blood. These results suggest that imatinib poorly penetrates the blood,brain barrier and has limited activity against CNS leukaemia. [source]

Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade glioma

CANCER, Issue 6 2004
Peter Hau M.D.
Abstract BACKGROUND Doxorubicin exhibits high efficacy in malignant glioma cell cultures. Nonetheless, as a standard formulation, doxorubicin has not been used clinically, due to poor penetration of the blood-brain barrier. Furthermore, doxorubicin is known to induce tumor resistance genes. To address both of these issues, the authors investigated the use of pegylated liposomal doxorubicin (CaelyxÔ; Essex Pharma, Munich, Germany) alone (Trial 1) and in combination with tamoxifen (Trial 2) in two sequentially performed nonrandomized prospective Phase II trials involving patients with recurrent high-grade glioma. METHODS Twenty patients were included in each trial. Progression-free survival at 6 months (PFS-6) and toxicity were the primary endpoints. Expression of the tumor resistance proteins multidrug resistance protein 1 (MDR-1) and multiple resistance protein (MRP) was evaluated by immunohistochemical methods and by sestamibi,single-photon emission computed tomography (SPECT). RESULTS The overall response rate (including cases of disease stabilization) was 40% in both Trial 1 and Trial 2. PFS-6 was 15%, and the median time to disease progression was 17 weeks. It is noteworthy that 40% of patients with Grade III tumors had long-term responses, which lasted for up to 3 years. There was no significant difference between Trial 1 and Trial 2 in terms of efficacy. Both regimens were well tolerated, with the main side effect being palmoplantar erythrodysesthesia. The authors found no correlation between clinical response and expression of tumor resistance genes or between clinical response and SPECT data. CONCLUSIONS Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma. None of the putative predictors for response that were evaluated proved to be significant in this setting. Cancer 2004. © 2004 American Cancer Society. [source]

Recent Approaches to Antifungal Therapy for Invasive Mycoses

CHEMMEDCHEM, Issue 3 2009
Bijoy
Abstract Antimycotic agents: Diverse classes of antimycotic drugs have been developed over the past decades with the goal of improving selectivity and efficacy. This review discusses both conventional and novel targets for antifungal agents and the possibility of vaccination in the treatment of invasive fungal infections. Invasive fungal infections with primary and opportunistic mycoses have become increasingly common in recent years and pose a major diagnostic and therapeutic challenge. They represent a major area of concern in today's medical fraternity. The occurrence of invasive fungal diseases, particularly in AIDS and other immunocompromised patients, is life-threatening and increases the economic burden. Apart from the previously known polyenes and imidazole-based azoles, newly discovered triazoles and echinocandins are more effective in terms of specificity, yet some immunosuppressed hosts are difficult to treat. The main reasons for this include antifungal resistance, toxicity, lack of rapid and microbe-specific diagnoses, poor penetration of drugs into sanctuary sites, and lack of oral or intravenous preparations. In addition to combination antifungal therapy, other novel antimycotic treatments such as calcineurin signaling pathway blockers and vaccines have recently emerged. This review briefly summarizes recent developments in the pharmacotherapeutic treatment of invasive fungal infections. [source]